Osteopontin facilitates ultraviolet B-induced squamous cell carcinoma development.
J Dermatol Sci
; 75(2): 121-32, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24888687
ABSTRACT
BACKGROUND:
Osteopontin (OPN) is a matricellular glycoprotein that is markedly expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses implicating its role in photocarcinogenesis.OBJECTIVE:
To determine whether OPN facilitates the development of cSCC and its function.METHODS:
cSCCs development was compared between wild-type (WT) and OPN-null mice subjected to UVB irradiation for 43 weeks. UVB-induced OPN expression was determined by Western blot, immunoprecipitation, ELISA, and semi-quantitative RT-PCR. Epidermal layer and TUNEL analyses assessed if OPN mediates UVB-induced epidermal hyperplasia or suppresses UVB-induced apoptosis of basal keratinocytes, respectively. In vitro experiments determined whether OPN enhances cell survival of UVB-induced apoptosis and its potential mechanisms. Immunohistochemical analyses of epidermis assessed the expression of CD44 and focal adhesion kinase (FAK), molecules that mediate OPN survival function.RESULTS:
Compared to female WT mice, OPN-null mice did not develop cSCCs. UVB irradiation stimulated OPN protein expression in the dorsal skin by 11h and remains high at 24-48h. OPN did not mediate UVB-induced epidermal hyperplasia; instead, it protected basal keratinocytes from undergoing apoptosis upon UVB exposure. Likewise, the addition of OPN suppressed UVB-induced OPN-null cSCC cell apoptosis, the activation of caspase-9 activity, and increased phosphorylation of FAK at Y397. Furthermore, the expression of CD44 and FAK in WT mice epidermis was greater than that of OPN-null mice prior to and during early acute UVB exposure.CONCLUSION:
These data support the hypothesis that chronic UVB-induced OPN expression protects the survival of initiated basal keratinocytes and, consequently, facilitates cSCC develop.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Raios Ultravioleta
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Carcinoma de Células Escamosas
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Transformação Celular Neoplásica
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Epiderme
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Osteopontina
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Neoplasias Induzidas por Radiação
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article